Structural Knowledge of HCV Envelope Protein Region Recognized by Broadly Neutralizing Antibodies

Abstract

Evaluation of: Krey T, Meola A, Keck Z, Damier-Piolle L, Foung S, Rey F. Structural basis of HCV neutralization by human monoclonal antibodies resistant to viral neutralization escape. PLoS Pathog. 9(5), e1003364 (2013). HCV infects 3% of the world’s population. In approximately 80% of infected individuals the infection becomes chronic, which is a major risk factor for liver cirrhosis and cancer. One important hurdle in HCV therapy is the high mutation rate of the virus. Indeed, the efficacy of current HCV therapy is notably limited by its dependency on the virus genotype and the potential emergence of resistant viruses. Nevertheless, some viral envelope epitopes cannot tolerate high variability without affecting viral fitness and thus constitute an interesting target for neutralizing antibodies. In this paper, Krey and colleagues report the crystal structure of the Fab fragments from two broadly reactive human neutralizing monoclonal antibodies in contact with their cognate epitopes that are resistant to viral escape. They identified the main contact residues that form a hydrophobic protrusion at the surface of the HCV envelope glycoprotein E2 and are involved in interactions with the HCV coreceptor CD81. Thus, this structural motif that contains these residues represents an interesting target for vaccine design.